We propose to produce monoclonal antibodies that are directed against a regulatory cell surface glycopeptide. This glycopeptide has been isolated from mouse cerebral cortex cells and has the capacity to inhibit both protein synthesis and cell division of "normal" cells propagated in culture. In contrast to the sensitivity of primary or culture-adapted cell lines to the glycoceptide inhibitor, transformed or malignant cells are highly resistant or completely refractory to the presence of this substance. The reason for the resistant nature of transformed cells is presently unknown, and the availability of monoclonal antibodies would be a powerful means to further study this phenomenon. Since we have already partially purified and characterized this glycopeptide and shown that its inhibitory action is mediated by nanogram quantities, F(ab) fragments of monoclonal IgG would provide a sensitive and dependable molecular probe. This would be used to determine if the glycopeptide, when added to sensitive or transformed cells, binds to the cell surface, is rapidly internalized or remains at the surface to induce a secondary messenger (similar to peptide hormone action). Radiolabeled F(ab) fragments could also be used to identify and quantitate the potential growth regulatory substance on the surfaces of both "normal" and transformed cells. Monoclonal antibodies could be used to enhance purification procedures as well as to identify the parent cell surface glycoprotein from which the inhibitory glycopeptide fragment was released. The feasibility of these procedures was recently established when we successfully showed that the biologically active glycopeptide was immunogenic in BALB/c mice and that a sensitive and accurate assay for the IgG could be developed. The availability of monoclonal antibodies to this regulatory glycopeptide could be valuable to elucidate the mechanisms of cell growth control and transformation events of tumor cells associated with their autonomy.